title: Subtoxic and toxic concentrations of benzene and toluene induce Nrf2-mediated antioxidative stress response and affect the central carbon metabolism in lung epithelial cells A549.
abstract: Since people in industrialized countries spend most of their time indoors, the effects of indoor contaminants such as volatile organic compounds become more and more relevant. Benzene and toluene are among the most abundant compounds in the highly heterogeneous group of indoor volatile organic compounds. In order to understand their effects on lung epithelial cells (A549) representing lung's first line of defense, we chose a global proteome and a targeted metabolome approach in order to detect adverse outcome pathways caused by exposure to benzene and toluene. Using a DIGE approach, 93 of 469 detected protein spots were found to be differentially expressed after exposure to benzene, and 79 of these spots were identified by MS. Pathway analysis revealed an enrichment of proteins involved in Nrf2-mediated and oxidative stress response glycolysis/gluconeogenesis. The occurrence of oxidative stress at nonacute toxic concentrations of benzene and toluene was confirmed by the upregulation of the stress related proteins NQO1 and SOD1. The changes in metabolism were validated by ion chromatography MS/MS analysis revealing significant changes of glucose-6-phosphate, fructose-6-phosphate, 3-phosphoglycerate, and NADPH. The molecular alterations identified as a result of benzene and toluene exposure demonstrate the detrimental effect of nonacute toxic concentrations on lung epithelial cells. The data provided here will allow for a targeted validation in in vivo models.
authors.affiliation: Helmholtz Centre for Environmental Research, Department of Proteomics, Leipzig, Germany.
authors.forename: Kalaimathi
authors.initials: K
authors.lastname: Murugesan
authors.forename: Sven
authors.initials: S
authors.lastname: Baumann
authors.forename: Dirk K
authors.initials: DK
authors.lastname: Wissenbach
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kliemt
authors.forename: Stefan
authors.initials: S
authors.lastname: Kalkhof
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Otto
authors.forename: Iljana
authors.initials: I
authors.lastname: Mögel
authors.forename: Tibor
authors.initials: T
authors.lastname: Kohajda
authors.forename: Martin
authors.initials: M
authors.lastname: von Bergen
authors.forename: Janina M
authors.initials: JM
authors.lastname: Tomm
mesh_terms: D001554:Benzene / Q000633:toxicity*; D002244:Carbon / Q000378:metabolism; D002460:Cell Line; D016000:Cluster Analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D020543:Proteome / Q000032:analysis / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D040901:Proteomics; D020545:Respiratory Mucosa / Q000166:cytology; D015398:Signal Transduction / Q000187:drug effects; D014050:Toluene / Q000633:toxicity*; D059551:Toxicity Tests, Subacute
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D020543:Proteome; D014050:Toluene; D002244:Carbon; D001554:Benzene
keywords: Benzene + toluene; Molecular toxicity; Two-dimensional differential gel electrophoresis; Western blot